Perineural invasion by prostate adenocarcinoma in needle biopsies predicts bone metastasis: Ten year data from the TROG 03.04 RADAR Trial

Abstract

Aims Perineural invasion (PNI) by prostatic adenocarcinoma is debated as a prognostic parameter. This study investigates the prognostic predictive value of PNI in a series of patients with locally advanced prostate cancer treated with radiotherapy and androgen deprivation using 10 years outcome data from the TROG 03.04 RADAR trial. Methods Diagnostic prostate biopsies from 976 patients were reviewed and the presence of PNI noted. Patients were followed for 10 years according to the trial protocol or until death. The primary endpoint for the study was time to bone metastasis. Secondary endpoints included time to soft tissue metastasis, transition to castration resistance, prostate cancer‐specific mortality and all‐cause mortality. Results PNI was detected in 449 cases (46%), with 234 cases (24%) having PNI in more than one core. The presence of PNI was significantly associated with higher ISUP grade, clinical T staging category, National Comprehensive Cancer Network risk group, and percent positive biopsy cores. The cumulative probability of bone metastases according to PNI status was significant over the 10 years follow‐up interval of the study (log‐rank test P < 0.0001). PNI was associated with all endpoints on univariable analysis. After adjusting for baseline clinicopathological and treatment factors, bone metastasis was the only endpoint in which PNI retained its prognostic significance (hazard ratio 1.42, 95% confidence interval 1.05–1.92, P = 0.021). Conclusions The association between PNI and the development of bone metastases supports the inclusion of this parameter as a component of the routine histology report. Further this association suggests that evaluation of PNI may assist in selecting those patients who should be monitored more closely during follow‐up.

MRI detected extaprostatic extension (EPE) in prostate cancer: Do all T3a patients have the same outcomes?

“…Moreover, the 10-year follow-up analysis of the TROG 03.04 RADAR cohort have shown strong association between PNI and bone metastasis after radiation and ADT treatment [22].…”

Sensory nerves: A driver of the vicious cycle in bone metastasis?

“…PNI is demonstrated in bone metastasis as well. A clinicopathological study reported that PNI is detected in 449 (46%) out of 976 patients with prostate cancer by diagnostic biopsies and importantly prostate cancer with PNI is significantly associated with increased development of bone metastasis compared to prostate cancer without PNI over 10 year follow-up interval [72] . Further, it is also described that PNI detected in the biopsy specimens is the most reliable predictive histopathological feature for bone metastasis, increasing the risk of bone metastasis 11-fold [73] .…”

The nervous system: Orchestra conductor in cancer, regeneration, inflammation and immunity

“…Interestingly, the clinical ramifications of the role of nerves in cancer go beyond treatment, as nerves could also be used to identify life‐threatening prostate cancers (that require aggressive therapeutic interventions) from indolent prostate cancers (that only require active surveillance). Nerve infiltration is indeed higher in high‐risk prostate cancer compared with low‐risk prostate cancer 31 and perineural invasion, which is associated with nerve infiltration, has recently been shown to be an independent predictor of metastatic progression in prostate cancer 36 . In addition, as nerve trunks in the prostate can be observed by using magnetic resonance imaging (MRI), nerve density determined by MRI could be a noninvasive way to identify aggressive prostate cancers at the time of diagnosis 37 .…”

“…Nerve infiltration is indeed higher in high‐risk prostate cancer compared with low‐risk prostate cancer 31 and perineural invasion, which is associated with nerve infiltration, has recently been shown to be an independent predictor of metastatic progression in prostate cancer. 36 In addition, as nerve trunks in the prostate can be observed by using magnetic resonance imaging (MRI), nerve density determined by MRI could be a noninvasive way to identify aggressive prostate cancers at the time of diagnosis. 37 Thus, in clinical terms, nerve involvement could be used for the establishment of cancer prognosis, to predict patient outcome, and in the treatment for preventing or interfering with neurosignaling.…”